Acute Graft versus Host Disease: Studies in Histology And the Role of Tissue Repair and Regeneration

Abstract

Acute graft-versus-host disease (aGvHD) occurs when donor T-lymphocytes attack host tissues; the disease can be life threatening. Recently, elevated circulating Follistatin (FS) was described in those expe- riencing aGvHD; higher concentrations of this factor were associated with poorer survival and greater risk for the disease. The mechanism behind these increased FS levels is unknown. As such, it is essential that we further study the tissue-specific expression of FS. As aGvHD greatly affects the intestinal tract, we hy- pothesize that studying FS expression in the intestinal tract will provide a better understanding of the role of FS in aGvHD. This study can be completed by a multi-step process. This paper focuses on the first step: the histological differences in the intestine of individuals with or without aGvHD. We did this by perform- ing Hematoxylin and Eosin Stains on aGvHD affected versus control intestinal mouse tissue and compared the tissue histology of the two groups. We found that aGvHD affected tissues appeared to have disorga- nized villi, in which the inter-villi distance varied significantly more than control tissues, in which the villi appeared to be more organized. This indicates that aGvHD causes an abnormality in organizational proteins that give rise to villi. This is of importance as an organizational abnormality may be the reason for the symptoms of aGvHD such as digestion problems and diarrhea. Now that our model is established and shows consistent differences in histology, tissues can be stained for FS, and FS signaling pathways can be interrogated using molecular arrays.